New potential target to treat obesity identified

New York: Scientists have discovered a new mechanism in the mouse-brain that can help regulate obesity triggered by consuming a high-fat diet and can also be used as a potential treatment. Consuming a high-fat diet results in changes in the brain that increases Rap1 gene, which is expressed in a variety of tissues, including the brain where it is involved in functions such as memory and learning.

Increase in Rap1 gene activity in turn leads to a decreased sensitivity to leptin — the ‘satiety hormone’ produced by fatty tissue that helps regulate body weight by inhibiting appetite — that sets the body on a path to obesity, the study said.

“This new mechanism involving Rap1 in the brain, may represent a potential therapeutic target for treating human obesity in the future,” said Makoto Fukuda, Assistant Professor at Baylor College of Medicine in Texas, US.

In the study, the researchers analysed the mouse Rap1 gene and selectively deleted the gene in a group of neurons in the hypothalamus — a region of the brain that is involved in regulating whole-body metabolism. While one group of mice were genetically engineered to lack the Rap1 gene, the other (control) group had a functional Rap1 gene.

The scientists then fed both group of mice to a high-fat diet in which 60 per cent calories came from fat. As expected, the control mice with a working Rap1 gene gained weight, but, in comparison, the mice that lacked Rap1 had markedly reduced body weight and less body fat.

Despite eating a high-fat diet, the mice lacking the Rap1 gene had not gained weight as a result of eating less as well as burning more body fat than mice with Rap1.

“These observations were associated with the hypothalamus producing more of a hormone that reduces appetite, called POMC, and less of hormones that stimulate appetite, called NPY and AgRP,” Fukuda added.

These mice also had lower levels of blood glucose and insulin than the controls.

Further, the mice that lacked Rap1 and ate a high-fat diet also did not develop leptin resistance, but were able to respond to leptin, and this was reflected in the hormone’s lower blood levels, the researchers concluded in the paper appearing in the journal– Cell Reports.